title: Intracellular antagonistic interaction between GnRH and gonadotrophin surge-inhibiting/attenuating factor bioactivity downstream of second messengers involved in the self-priming process.
abstract: The antagonistic control of LH concentrations by GnRH and the putative ovarian factor gonadotrophin surge-inhibiting or -attenuating factor (GnSIF/AF) was studied by perifusion of female rat pituitary glands in vitro. LH release and GnRH self-priming were measured in response to five (0.32-10 nmol l-1) or three (10 nmol l-1) 10 min pulses of GnRH. In the latter case, pulses were preceded by five 10 min pulses of either 1 mmol 8-bromo-cAMP l-1 plus 10 mmol theophylline l-1 or 1 mumol phorbol 12-myristate 13-acetate l-1. The stimulations were carried out in the presence or absence of steroid-free bovine follicular fluid, which possesses GnSIF/AF bioactivity, to study the effect of GnSIF/AF on the self-priming process during successive stimulations by GnRH. First, the effect of follicular fluid was studied on GnRH-induced LH release from pituitary glands collected during the ovarian cycle. Only when a clear self-priming effect was evident, as on day 2 of dioestrus and the day of pro-oestrus, follicular fluid antagonized the self-priming effect of GnRH. Second, when glands on day 2 of dioestrus were used, self-priming was displayed by various combinations of GnRH and follicular fluid. The pulses with the lowest concentrations of GnRH together with a high concentration of follicular fluid, however, led to stable low amplitude LH pulses. Finally, priming of the pituitary LH response to GnRH with 8-bromo-cAMP plus theophylline or phorbol 12-myristate 13-acetate was inhibited by follicular fluid. These results confirm the control of LH release by GnRH and GnSIF/AF bioactivity. The effect of GnSIF/AF in follicular fluid is most pronounced on the days before the LH surge, showing evidence of its important role in maintaining low LH concentrations during this period. GnSIF/AF neutralizes downstream actions of second messengers involved in GnRH self-priming.
authors.affiliation: Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Sylvius Laboratories, University of Leiden, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Tijssen
authors.forename: M N
authors.initials: MN
authors.lastname: Helder
authors.forename: Z W
authors.initials: ZW
authors.lastname: Chu
authors.forename: J
authors.initials: J
authors.lastname: de Koning
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D004971:Estrus / Q000378:metabolism; D005260:Female; D015571:Follicular Fluid / Q000378:metabolism; D042341:Gonadal Hormones; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000096:biosynthesis*; D009924:Organ Culture Techniques; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015290:Second Messenger Systems; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
chemical_list: D042341:Gonadal Hormones; D011506:Proteins; C080538:attenuin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D013806:Theophylline; D013755:Tetradecanoylphorbol Acetate